TABLE 5.

Adaptive Adjuvant Treatment Escalation Trials

Trial	Inclusion Criteria	Treatment Arms	Primary Objective: iDFS	n
Katherine Phase III	cT1-4/N0-3/M0 (excluding T1a or T1bN0) HER2-positive with residual disease NACT: 9 weeks minimum of taxane and trastuzumab, 16 weeks or 6 cycles	T-DM1 once every 3 weeks ×14	3-year iDFS, 88%	743
		Trastuzumab once every 3 weeks ×14	3-year iDFS, 77%	743
COMPASS HER2-RD Phase III	cT1-4/N0-3/M0 (excluding T1a/bN0) HER2-positive with residual disease Any ER, but if ER+ must be LN+ NACT: minimum of 16 weeks or 6 cycles of preoperative taxane and trastuzumab-based chemotherapy	T-DM1/placebo once every 3 weeks ×14	NA
		T-DM1/tucatinib once every 3 weeks ×14	NA
Astefania Phase III	cT4/anyN/M0, any cT/N2-3/M0, cT1-3/N0-1/M0 (excluding cT1mi/T1a/T1b/N0) HER2-positive with residual disease NACT: minimum 9 weeks of taxane and trastuzumab	T-DM1/placebo once every 3 weeks ×14	NA
		T-DM1 + atezolizumab once every 3 weeks ×14	NA
DESTINY Breast05 Phase III	cT4/N0-3/M0 or T1-3/N2-3/M0 or cT1-3/N0-1/M0 but with positive LN at surgery (ypN1-3) HER2-positive with residual disease (must have completed NACT)	T-DM1	NA
		T-DXd	NA

NOTE. The experimental treatments are shown in bold.

Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; iDFS, invasive disease-free survival; LN, lymph nodes; NA, not available; NACT, neoadjuvant chemotherapy; T-DM1, trastuzumab-DM1; T-DXd, trastuzumab deruxtecan.